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Mu and delta receptors mediate morphine effects on phagocytosis by murine peritoneal macrophages
Nilka Tomassini1, Fernando L Renaud, Sabita Roy
1Biology Department, University of Puerto Rico, POB 23360 Río Piedras Campus, San Juan 00931-3360, Puerto Rico.
Abstract:
Studies with selective opioid agonists show that mu- and delta(2)-opioid receptors, but not kappa, are involved in opioid inhibition of phagocytosis in elicited murine macrophages. All mu and delta(2) agonists tested had similar maximal effects on phagocytosis, and all dose-response curves suggest positive cooperativity. In addition, mu and delta antagonists antagonized the effect of both mu and delta agonists. Furthermore, in mu-opioid receptor knockout mice (MORKO), we observed a decrease in potency and maximal effect for a delta agonist. These data suggest that mu and delta receptors are not only involved in the modulation of phagocytosis in macrophages, but they also affect each other's activity by an unknown cooperative mechanism.
Insights
Mu and delta(2)-opioid receptors, not kappa, inhibit macrophage phagocytosis. These opioid receptors modulate each other
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Opioid receptors are known to modulate immune cell functions.
- Phagocytosis is a critical immune process involving the engulfment of pathogens by immune cells.
Purpose of the Study:
- To investigate the specific roles of mu-, delta-, and kappa-opioid receptors in the inhibition of phagocytosis in murine macrophages.
- To explore the potential interactions and cooperative mechanisms between mu- and delta-opioid receptors in regulating phagocytosis.
Main Methods:
- Utilized selective opioid agonists and antagonists to study their effects on phagocytosis in elicited murine macrophages.
- Employed mu-opioid receptor knockout (MORKO) mice to assess the impact of receptor absence on agonist efficacy.
- Analyzed dose-response curves to determine receptor involvement and cooperativity.
Main Results:
- Mu- and delta(2)-opioid receptors, but not kappa receptors, were found to inhibit phagocytosis.
- All tested mu and delta(2) agonists demonstrated similar maximal effects, with dose-response curves indicating positive cooperativity.
- Mu- and delta-opioid antagonists effectively blocked the effects of both mu- and delta-opioid agonists.
- In MORKO mice, a delta-opioid agonist showed reduced potency and maximal effect, suggesting mu-delta receptor interaction.
Conclusions:
- Mu- and delta-opioid receptors play significant roles in modulating macrophage phagocytosis.
- Evidence suggests a cooperative mechanism between mu- and delta-opioid receptors, where they influence each other's activity.
- Further research is needed to elucidate the precise molecular mechanisms underlying this opioid receptor cross-talk in immune cells.